C4951012 - BHV3000-407: A Phase 4, Randomized, Double-blind, Placebo controlled Study to Evaluate the Efficacy and Tolerability of Rimegepant for the Prevention of Migraine in Adults with a History of Inadequate Response to Oral Preventive Medications

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Mar 2023 → 9 Jul 2025

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-513270-21-00

EudraCT number

2022-001176-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others

To compare the efficacy of rimegepant to placebo as an EOD dosing regimen for prophylaxis in adults with a history of inadequate response to agents across 2-4 categories of recognized, orally-administered migraine preventive medications as measured by the mean reduction from the Observation Phase in the number of migraine days per month (28 days) over the entire DBT Phase.

Secondary objectives 5

1. To compare the proportion of subjects with ≥ 50% reduction from the Observation Phase in the number of migraine days of moderate or severe headache pain intensity per month over the entire DBT Phase (Weeks 1 to 12) between rimegepant and placebo.
2. To compare the mean reduction from the Observation Phase in the number of migraine days per month in the first 4 weeks of the DBT Phase between rimegepant and placebo.
3. To compare the mean reduction from the Observation Phase in the number of migraine days per month in the last 4 weeks of the DBT Phase between rimegepant and placebo.
4. To compare the mean change from baseline in the Migraine-Specific Quality-of-Life Questionnaire v 2.1 (MSQ) restrictive role function domain score at Week 12 of the DBT Phase between rimegepant and placebo.
5. To compare the mean change from baseline in Migraine Interictal Burden Scale (MIBS) score at Week 12 of the DBT Phase between rimegepant and placebo.

Conditions and MedDRA coding

migraine headaches with or without aura

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Target Population: Minimum 1 year documented history of migraines (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition.3 Per self-report, with confirmation from Investigator / supporting medical record, subjects must have: a. Migraine attacks present for more than 1 year from the Screening Visit b. Age of onset prior to 50 years of age c. Migraine attacks lasting about 4–72 hours, if untreated d. 4 to 14 migraine days, on average, across the 3 months prior to the Screening Visit e. 4 to 14 migraine days during the 28-day Observation Phase f. Subjects must be able to distinguish migraine attacks from tension headaches g. Prior inadequate response, within 10 years of the Screening Visit, to agents across 2-4 categories of recognized, orally-administered migraine-preventive medications where at least one example of prior inadequate response is due to lack of efficacy or prior intolerance (not contraindication)
2. Age and Reproductive Status: a) Subjects ≥18 years-old b) Subject meets reproductive criteria. Refer to Section 16.6 c) At the Baseline Visit, prior to dispensing investigational study drug, WOCBP must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) before dosing with study drug. For further inclusion criteria, please refer to the Protocol

Exclusion criteria 7

1. Target Disease Exclusion a) History of cluster headaches, basilar migraine (with aura), or hemiplegic migraine b) Current medication overuse headaches c) 15 or more headache days (migraine or non-migraine) per month in any of the 3-months prior to the Screening Visit or during the 28-day Observation Phase d) 7 or more non-migraine headache days per month, on-average, across the 3-months prior to the Screening Visit or during the 28-day Observation Phase e) Inadequate response to agents across > 4 categories of recognized, orally administered, migraine-preventive medications
2. Medical History and Current Diseases: a) History of gastric or small intestinal surgery or disease or conditions that causes malabsorption b) BMI ≥ 35kg/m2 c) Alcohol or drug abuse within the past 12 months or subjects with any significant substance use disorder within the past 12 months from the date of the Screening Visit d) Current diagnosis of major depressive disorder requiring treatment with an atypical antipsychotic e) Current diagnosis of schizophrenia, bipolar disorder, or borderline personality disorder f) Other major psychiatric disorder that might interfere with the ability to properly report clinical outcomes g) Major depressive disorder or any anxiety disorder which requires more than 1 daily medication for each disorder. h) Major depressive episode within last 12 months prior to the Screening Visit. i) Subjects who meet criteria for C-SSRS Suicidal Ideation Items 4 or 5 within the last 12 months prior to the Screening Visit, OR subjects who endorse any of the 5 C-SSRS Suicidal Behavior Items within the last 10 years prior to the Screening Visit, OR subjects who present a serious risk of suicide j) Active chronic pain syndromes k) Other pain syndromes (including trigeminal neuralgia), dementia, significant neurological disorders other than migraine l) Current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease m) Myocardial infarction, acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), cardiac surgery, stroke or transient ischemic attack within 6 months prior to the Screening Visit n) Uncontrolled hypertension (high blood pressure). o) Any unstable medical conditions (e.g., history of congenital heart disease, arrhythmia, or cancer) p) Positive drug screen for drugs of abuse that in the Investigator's judgment is medically significant, in that it would impact the safety of the subject or the interpretation of the study results.
3. Allergies and Adverse Drug Reactions: History of drug or other allergy which, in the opinion of the investigator, makes the subject unsuitable for participation in the study.
4. Sex and Reproductive Status WOCBP who are unwilling or unable to use required contraception a) Women who are pregnant or breastfeeding b) Women with a positive pregnancy test at Screening Visit
5. ECG and Laboratory Test Findings - as specified in the protocol.
6. Prohibited Medications and Devices a) Recognized migraine-preventive medication taken within 30 days prior the Screening (with exceptions) b) Non-Narcotic Analgesics or paracetamol taken 15 days per month during the 3 months prior to the Screening Visit c) Any device for migraine prevention or treatment within 3 months prior to the Screening Visit d) Ergotamine taken 10 days per month on a regular basis for 3 months in the year prior to the Screening Visit e) Narcotic, such as opioid or barbiturate taken for 4 days per month during the 3 months prior to the Screening Visit f) Permitted acute migraine medication taken 15 days per month for a non-headache indication during the 3 months (12 weeks) prior to the SV
7. Other a) Non-compliance with or inability to complete eDiary during Observation Phase. Subjects with less than 24 completed eDiary reports during 28 days in the Observation Phase b) Exposure to non-biological investigational agents within 30 days prior to the Screening c) Exposure to biological investigational agents within 6 months prior to the Screening d) Previous enrollment in any multiple dose BHV3000 (rimegepant) study. Subjects may be considered for BHV3000-407 if the subject participated in any of the following single-dose studies: BHV3000-301, BHV3000-302, BHV3000-303, but did not participate in any multiple dose rimegepant study. e) Participation in any other clinical study while participating in this clinical study. f) Past participation in a clinical study within 30 days prior to the Screening Visit g) Failure to complete the Baseline Visit within the timeframe specified in the schedule of assessments h) The subject is clinically unsuitable to participate i) Site staff directly involved in the conduct of the study and their family, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. For further exclusion criteria, please refer to the Protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from the Observation Phase in the number of migraine days per month over the entire double-blind treatment (DBT) Phase.

Secondary endpoints 5

1. Proportion of subjects with ≥ 50% reduction from the Observation Phase in the number of migraine days of moderate or severe headache pain intensity per month over the entire DBT Phase (Weeks 1 to 12).
2. Mean change from the Observation Phase in the number of migraine days per month in the first 4 weeks (Weeks 1 to 4) of the DBT Phase.
3. Mean change from the Observation Phase in the number of migraine days per month in the last 4 weeks (Weeks 9 to 12) of the DBT Phase.
4. Mean change from baseline in the MSQ restrictive role function domain score at Week 12 of the DBT Phase.
5. Mean change from baseline in the MIBS score at Week 12 of the DBT Phase.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 9

Locations

9 EU/EEA countries · 71 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 77 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications